BACKGROUND

Available evidence from randomized controlled trials supports the use of glucosamine sulfate in the treatment of osteoarthritis, particularly of the knee. It is believed that the sulfate moiety provides clinical benefit in the synovial fluid by strengthening cartilage and aiding glycosaminoglycan synthesis. If this hypothesis is confirmed, it would mean that only the glucosamine sulfate form is effective and non-sulfated glucosamine forms are not effective.

Glucosamine is commonly taken in combination with chondroitin, a glycosaminoglycan derived from articular cartilage. Use of complementary therapies, including glucosamine, is common in patients with osteoarthritis, and may allow for reduced doses of non-steroidal anti-inflammatory agents.

EVIDENCE TABLE

Conditions

Usesdisclaimer: These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Grade*

Knee osteoarthritis (mild-to-moderate)

Based on human research, there is good evidence to support the use of glucosamine sulfate in the treatment of mild-to-moderate knee osteoarthritis. Most studies have used glucosamine sulfate supplied by one European manufacturer (Rotta Research Laboratorium), and it is not known if glucosamine preparations made by other manufacturers are equally effective. Although some studies of glucosamine have not found benefits, these have either included patients with severe osteoarthritis or used products other than glucosamine sulfate. The evidence for the effect of glycosaminoglycan polysulphate is conflicting and merits further investigation. More well-designed clinical trials are needed to confirm safety and effectiveness, and to test different formulations of glucosamine.

A

Osteoarthritis (general)

Several human studies and animal experiments report benefits of glucosamine in treating osteoarthritis of various joints of the body, although the evidence is less plentiful than that for knee osteoarthritis. Some of these benefits include pain relief, possibly due to an anti-inflammatory effect of glucosamine, and improved joint function. Overall, these studies have not been well designed. Although there is some promising research, more study is needed in this area before a firm conclusion can be made.

B

Chronic venous insufficiency

"Chronic venous insufficiency" is a syndrome that includes leg swelling, varicose veins, pain, itching, skin changes, and skin ulcers. The term is more commonly used in Europe than in the United States. Currently, there is not enough reliable scientific evidence to recommend glucosamine in the treatment of this condition.

C

Diabetes (and related conditions)

Early research suggests that glucosamine does not improve blood sugar control, lipid levels, or apolipoprotein levels in diabetics. Additional research is needed in this area.

C

Inflammatory bowel disease (Crohn's disease, ulcerative colitis)

Preliminary research reports improvements with N-acetyl glucosamine as an added therapy in inflammatory bowel disease. Further scientific evidence is necessary before a strong recommendation can be made.

C

Pain (leg pain)

Preliminary human research reports benefits of injected glucosamine plus chondroitin in the treatment of leg pain arising from advanced lumbar degenerative disc disease. Further scientific evidence is necessary before a firm recommendation can be made.

C

Rehabilitation (after knee injury)

Glucosamine has been given to athletes with acute knee injuries. Although glucosamine did not improve pain, it did help improve flexibility. Additional research is needed to confirm these early findings.

C

Rheumatoid arthritis

Early human research reports benefits of glucosamine in the treatment of joint pain and swelling in rheumatoid arthritis. In other research, glucosamine did not exert anti-rheumatic effects, but it did improve symptoms of the disease. However, this is early information, and additional research is needed before a conclusion can be drawn. The treatment of rheumatoid arthritis can be complicated, and a qualified healthcare provider should follow patients with this disease.

C

Temporomandibular joint (TMJ) disorders

There is a lack of sufficient evidence to recommend for or against the use of glucosamine (or the combination of glucosamine and chondroitin) in the treatment of temporomandibular joint disorders.

C

High cholesterol

Glucosamine does not appear to alter LDL or HDL levels in patients with chronic joint pain or diabetes.

D

*Key to grades: A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).

TRADITION

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below. AIDS, athletic injuries, back pain, bleeding esophageal varices (blood vessels in the esophagus), cancer, congestive heart failure, depression, fibromyalgia, kidney stones, migraine headache, immunosuppression, osteoporosis, pain, psoriasis, skin rejuvenation, spondylosis deformans (growth of bony spurs on the spine), topical hypopigmenting agent (combination product containing multiple ingredients), wound healing.

DOSING

disclaimer: The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

In most available studies, 500 milligrams of glucosamine sulfate has been taken by mouth as tablets or capsules three times daily for 30 to 90 days. Once daily dosing as 1.5 grams (1,500 milligrams) has also been used. Limited research has used 1,500 milligrams daily as a crystalline powder for oral solution or 500 milligrams of glucosamine hydrochloride three times daily. Dosing of 20 milligrams per kilogram of body weight daily has also been recommended in some publications. One study used a dose of 2,000 milligrams per day for 12 weeks.

Another kind of glucosamine that has been used is a topical form in combination with chondroitin for a four-week period. Safety and effectiveness of these formulations are not clearly proven.

Glucosamine hydrochloride provides more glucosamine than glucosamine sulfate, although this difference likely does not matter when products are prepared to provide a total of 500 milligrams of glucosamine per tablet.

Children (younger than 18 years)

There is not enough scientific evidence to recommend the use of glucosamine in children.

Research in children has shown that there could be a relationship between the ingestion of MSM (methylsulfonylmethane) and autism; whether it is beneficial or harmful is unclear. MSM is often marketed with glucosamine as a dietary supplement and at this time should be avoided in children.

SAFETY

disclaimer: The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Since glucosamine can be made from the shells of shrimp, crab, and other shellfish, people with shellfish allergy or iodine hypersensitivity may have an allergic reaction to glucosamine products. However, some research suggests that there is not enough shrimp allergen in glucosamine supplements to trigger reactions in patients who are allergic to shrimp. Nevertheless, caution is warranted. A serious hypersensitivity reaction including throat swelling has been reported with glucosamine sulfate. There are reported cases suggesting a link between glucosamine/chondroitin products and asthma exacerbations.

Side Effects and Warnings

In most human studies, glucosamine sulfate has been well tolerated for 30 to 90 days.

Side effects may include upset stomach, drowsiness, insomnia, headache, skin reactions, sun sensitivity, and nail toughening. There are rare reports of abdominal pain, loss of appetite, vomiting, nausea, flatulence (gas), constipation, heartburn, and diarrhea. Based on several human cases, temporary increases in blood pressure and heart rate, as well as palpitations, may occur with glucosamine/chondroitin products. Based on animal research, glucosamine theoretically may increase the risk for eye cataract formation.

It remains unclear if glucosamine alters blood sugar levels. Several human studies suggest that glucosamine taken by mouth has no effects on blood sugar, while other research reports mixed effects on insulin. When glucosamine is injected, it appears to cause insulin resistance and endothelial dysfunction. Preliminary studies show no effect on mean hemoglobin A1c concentrations in patients with type 2 diabetes mellitus. Caution is advised in patients with diabetes or hypoglycemia and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider and medication adjustments may be necessary.

In theory glucosamine may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.

In several human cases, abnormally high amounts of protein were found in the urine of patients receiving glucosamine/chondroitin products. The clinical meaning of this is unclear. Glucosamine is removed from the body mainly in the urine, and elimination of glucosamine from the body is delayed in people with reduced kidney function. Acute interstitial nephritis, a condition that causes the kidneys to become swollen and possibly dysfunctional, has been reported in a patient taking glucosamine. Increased blood levels of creatine phosphokinase may occur with glucosamine/chondroitin, which may be due to impurities in some products. This may alter certain laboratory tests measured by healthcare providers.

Early data suggest that glucosamine may modulate the immune system, although the clinical relevance of this is not clear.

Pregnancy and Breastfeeding

Glucosamine is not recommended during pregnancy or breastfeeding due to lack of scientific evidence.

INTERACTIONS

disclaimer: Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Herbs and Dietary Supplements

In theory, glucosamine may decrease the effectiveness of herbs or supplements that lower blood sugar levels. Caution is advised when using herbs or supplements that may alter blood sugar.

Based on limited human study, side effects of glucosamine may be increased when used at the same time as diuretic herbs or supplements.

In theory, glucosamine may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding

There are preliminary reports that use of glucosamine with vitamin C, bromelain, chondroitin sulfate, or manganese may lead to increased beneficial glucosamine effects on osteoarthritis. Simultaneous use with fish oil may have additive beneficial effects in the treatment of psoriasis, based on preliminary research.

ATTRIBUTION

This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Ask the Expert

Professor Asgar Ali Kalla completed his MBChB (Bachelor of Medicine and Bachelor of Surgery) degree in 1975 at the University of Cape Town and his FRCP in 2003 in London.
Professor Ali Kalla is the Isaac Albow Chair of Rheumatology at the University of Cape Town and also the Head of Division of Rheumatology at Groote Schuur Hospital.
He has participated in a number of clinical trials for rheumatology and is active in community outreach.
Prof Ali Kalla is an expert in Arthritis for Health24.

posted on 21/01/2018

posted on 16/01/2018

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